licensespc_tr0725-013-001_29042015094056

IPAR

Public Assessment Report for aTraditional Herbal Medicinal Product

for Human Use

Echinaforce Sore Throat Spray

TR0725/013/001

Bioforce (UK) Ltd

December 2014

Health Products Regulatory Authority

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Date Printed 29/04/2015 CRN 2096306 page number: 1

I INTRODUCTION

Specific provisions were introduced for traditional herbal medicinal products (THMPs) in accordance with theTraditional Herbal Medicinal Products Directive (2004/24/EC). The national regulations, the Medicinal Products(Control of Placing on the Market) Regulations 2007 (S.I. No. 540 of 2007) which implement this Directive came intoforce on 23rd July 2007. Consequently the HPRA has established the Traditional Herbal Medicinal ProductsRegistration Scheme.

The Public Assessment Report reflects the scientific conclusion reached by the Health Products Regulatory Authority(HPRA) at the end of the evaluation process and provides a summary of the grounds for approval of a Certificate ofTraditional Use Registration for a specific traditional herbal medicinal product for human use. It is made available bythe HPRA for information to the public, after deletion of commercially sensitive information. The legal basis for itscreation and availability is contained in Article 21 of EC Directive 2001/83/EC, as amended by Directive 2004/27/ECand Directive 2004/24/EC. It is a concise document which highlights the main parts of the documentation submitted bythe applicant and the scientific evaluation carried out by the HPRA leading to the approval of the traditional herbalmedicinal product for marketing in Ireland.

Based on the review of the data on quality, safety and traditional use, the HPRA has granted Bioforce (UK) Ltd aCertificate of Traditional Use Registration for Echinaforce Sore Throat Spray, containing tinctures of fresh Echinaceapurpurea (L.) Moench herb, fresh Echinacea purpurea (L.) Moench root and fresh Sage leaves (Salvia officinalis (L.)folium).

This application was submitted as a standard application according to Article 16c of Directive 2001/83/EC, asamended, as part of the Traditional Herbal Medicinal Product Registration Scheme.

The Summary of Product Characteristics (SmPC) for this traditional herbal medicinal product is available on theHPRA’s website.

II QUALITY ASPECTS

This application is for Echinaforce Sore Throat Spray. The active ingredients of Echinaforce Sore Throat Spray areextracts (tinctures) obtained from fresh Echinacea purpurea (L.) Moench herb, fresh Echinacea purpurea (L.) Moenchroot and fresh Sage leaves (Salvia officinalis (L.) folium) using ethanol as the extraction solvent.

Each 2 spray dose contains:• 379.9 mg of tincture from fresh Echinacea purpurea (L.) Moench herb (1:12-13). Extraction solvent:

ethanol 65% V/V• 20.0 mg of tincture from fresh Echinacea purpurea (L.) Moench root (1: 11-12). Extraction solvent:

ethanol 65% V/V• 189.2 mg of tincture from fresh Sage leaves (Salvia officinalis (L.) folium) (1:17-18). Extraction

solvent: ethanol 68% V/V

1 spray � 0.22 ml

II.1 S.1 Herbal Substance

There are three herbal substances in Echinaforce Sore Throat Spray:

� Echinacea purpurea herba (herb)� Echinacea purpurea radix (root) and� Salvia officinalis (L.) folium (Sage leaves).

The herbal substance specifications are considered adequate to control the quality and meet current appropriaterequirements. The specifications are supported by the batch data provided.


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II.2 S.2 Herbal preparation

There are three herbal preparations in Echinaforce Sore Throat Spray:

� tincture from fresh Echinacea purpurea (L.) Moench herb (1:12-13)� tincture from fresh Echinacea purpurea (L.) Moench root (1:11-12)� tincture from fresh Salvia officinalis (L.) folium (Sage leaves) (1:17-18)

The herbal preparations are manufactured in accordance with the principles of good manufacturing practice (GMP).The herbal preparation specification is considered adequate to control the quality and meets current pharmacopoeialrequirements. Batch analytical data demonstrating compliance with this specification has been provided.

II.3 Medicinal product

P.1 Composition

The product is a brown to yellow-green, clear liquid oromucosal spray with an aromatic odour of peppermint and afresh, slightly bitter taste:Each 1 ml of liquid contains:

It also contains the following excipients; Sucrose laurate (E473), Soy lecithin, Ethanol, Peppermint oil, Sorbitol liquid(non crystallising).

P.2 Pharmaceutical Development

The product is an established pharmaceutical form and its development is adequately described.

P.3 Manufacture of the Product

The product is manufactured in accordance with the principles of GMP at suitably qualified manufacturing sites. Themanufacturing process has been validated according to relevant European Guidelines and the process is considered tobe sufficiently validated.

P.4 Control of Other Substances (Excipients)

All excipients comply with their respective Ph. Eur. Monographs, apart from sucrose laurate (E473) and soy lecithinwhich are adequately controlled by the manufacturer’s in-house specifications.All excipients are from non-animal and non-human sources, and, therefore, pose no TSE risk.

P.5 Control of Finished Product

The Finished Product Specification is satisfactory. The tests and control limits are justified with respect to conventionalpharmaceutical requirements and are considered appropriate for this type of product.

Tincture of fresh Echinacea purpurea (L.) Moenchherb (1:12-13). Extraction solvent: ethanol 65% v/v

863.3 mg

Tincture of fresh Echinacea purpurea (L.) Moench root(1:11-12). Extraction solvent: ethanol 65% v/v

45.5 mg

Tincture of fresh Sage leaves [Salvia officinalis (L.)folium] (1:17-18). Extraction solvent: ethanol 68% v/v.

430.0 mg


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The analytical methods used are described in sufficient detail and are supported by validation data.

Batch analytical data for a number of batches from the proposed production sites have been provided, and demonstratethe ability of the manufacturer to produce batches of finished product of consistent quality.

P.6 Packaging material

The finished product is packaged in 30 ml, brown, hydrolytic glass Type III (Ph.Eur.) flasks with an air pump andadaptor. The flasks are inserted into a cardboard carton with a patient leaflet.Suitable specifications have been provided by the packaging suppliers and it has been confirmed that all primarypackaging materials comply with Directive 2008/39/EC.

P.7 Stability of the Finished Product

Stability data on the finished product in the proposed packaging have been provided in accordance with EU guidelinesdemonstrating the stability of the product for 30 months in an unopened container and 2 months after first opening thecontainer. The product does not require any special storage conditions.

II.4 Conclusion on quality

The important quality characteristics of the product are well-defined and controlled. Satisfactory pharmaceuticaldocumentation has been provided, assuring consistent quality of Echinaforce Sore Throat Spray.

III NON-CLINICAL ASPECTS

Echinaforce Sore Throat Spray is a traditional herbal medicinal product as defined by Article 16a(1) of Directive2001/83/EC as amended.

An expert report on safety has been provided which includes an appropriate review of the available literature.

The Echinaforce extract contained in Echinaforce Sore Throat Spray has been shown to be non-mutagenic in aSalmonella typhimurium reverse mutation assay up to a dose of 5000 mcg/plate. The Sage extract contained inEchinaforce Sore Throat Spray has also been shown to be non-mutagenic in a Salmonella typhimurium reversemutation assay up to a dose of 5000 mcg/plate.

Tests on reproductive toxicity, genotoxicity and carcinogenicity have not been performed with Echinaforce Sore ThroatSpray.

Given the type of application and limited data available, it is not possible to assess if the safety package for thephytochemical constituents of Echinaforce Sore Throat Spray are acceptable to the standards of today’s GLP and safetytesting requirements.However, it can be concluded that overall the information presented demonstrating traditional use is considered to beacceptable and the lack of provision of a complete standard safety package is in line with the EMA ‘Guideline on Non-clinical Documentation for Herbal Medicinal Products in Applications for Marketing Authorisation (bibliographicaland mixed applications) and in Applications for Simplified Registration’ (EMEA/HMPC/32116/05).

An environmental risk assessment is not required for herbal medicinal products according to guidanceCPMP/SWP/4447/00.


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IV CLINICAL ASPECTS

This is a national application submitted by Bioforce (UK) Ltd under Article 16a of Directive 2001/83/EC, as amended.

Echinaforce Sore Throat Spray is a traditional herbal medicinal product used to relieve sore throats associated withcoughs, colds and flu-like illnesses, exclusively based on long-standing use. This product is indicated for use in adultsand older people over 18 years.

IV.1 Clinical Efficacy

There is no requirement under the Traditional Herbal Registration scheme to prove scientifically that the product isefficacious, the registration is based exclusively upon the longstanding use of Echinaforce Sore Throat Spray as atraditional herbal medicine and not upon data generated from clinical trials.

Article 16c1(c) of Directive 2001/83/EC requires the applicant to provide bibliographic or expert evidence to show thatthe medicinal product in question, or a corresponding product, has been in medicinal use throughout a period of at least30 years, including at least 15 years within the Community. With regard to this traditional use data, the requirements ofArticle 16c1(c) have been met.

The efficacy of this traditional herbal medicinal product is plausible on the basis of long standing use and experience.

The indication proposed for Echinaforce Sore Throat Spray is in line with traditional indications recorded and hence,compatible with the requirements of the Traditional Herbal Medicinal Products Directive 2004/24/EC.

IV.2 Clinical Safety

In accordance with Article 16c1(d) the applicant has provided a bibliographic review of the safety data together with anexpert report. The important safety information relevant to this product is as follows.

The use of this product in persons below 18 years of age is not recommended because a safe use has not beensufficiently documented.

The recommended dose should not be exceeded.

This product should not be used for more than 7 days. If symptoms worsen during the use of the product or persist formore than 7 days, a doctor or pharmacist should be consulted. Patients should consult a doctor if they have difficultyswallowing or breathing, if their sore throat is severe or is accompanied by high fever, headache, nausea or vomiting.

Because of their immuno-modulatory activity, Echinacea extracts must not be used in cases of progressive systemicdisorders (tuberculosis, sarcoidosis), autoimmune diseases (e.g. collagenoses, multiple sclerosis), immunodeficiences(e.g. HIV infections, AIDS), immunosuppression (e.g. oncological cytostatic therapy, history of organ or bone marrowtransplant) and diseases of the white blood cell system (e.g. agranulocytosis, leukaemias). There is also a possible riskof anaphylactic reactions in atopic patients. Atopic patients should consult their doctor before using Echinacea.

This product contains 40 – 47 vol % ethanol (alcohol). This corresponds to 163 mg alcohol which is equivalent to 4.1ml beer or 1.7 ml wine per dose (2 sprays). This may be harmful for those suffering from alcoholism. It should be takeninto account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease orepilepsy. This product should not be used with other medicines known to interact with alcohol (e.g. metronidazole).

This product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take thismedicine.

This product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactosemalabsorption or sucrase-isomaltase insufficiency should not take this medicine.


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No interaction studies have been performed with this product. This product should not be used at the same time asimmunosuppressant medications. The intake of Sage folium preparations might influence the effect of medicinalproducts acting via the GABA receptor (e.g. barbiturates, benzodiazepines), even if not seen clinically. Therefore usewith such medicinal products is not recommended

There are no or limited amount of data from the use of Echinaforce Sore Throat Spray in pregnant women. Animalstudies are insufficient with respect to reproductive toxicity. Echinaforce Sore Throat Spray is not recommended duringpregnancy. There is insufficient information on the excretion of Echinaforce Sore Throat Spray or its metabolites inhuman milk. A risk to newborns or infants cannot be excluded. Echinaforce Sore Throat Spray should not be usedduring breast-feeding. Studies on the effects on fertility have not been performed with this product.

No studies on the effects on the ability to drive and use machines have been performed.

This product may cause side effects. These include rash inside the mouth or a burning sensation, skin rash, hives,swelling of the face or skin, blistering of the skin, mouth, eyes or groin, difficulty breathing, asthma or anaphylacticshock.

There have been isolated reports suggesting an association with Echinacea products and autoimmune diseases such asmultiple sclerosis, erythema nodosum, low platelet count, Evans syndrome and Sjogren syndrome.

A decrease in the number of white blood cells may occur with long-term use (more than 8 weeks).

Overdose of this product may result in alcohol intoxication. The amount of alcohol in a full bottle (11 g in 30 ml whichis equivalent to a small glass of wine) may result in alcohol intoxication and should be treated accordingly.

For Sage leaves overdose has been reported to cause a sense of heat, fast heart rate, vertigo and seizures after an intakecorresponding to more than 15 g sage leaves (equivalent to between 38 and 66 doses of this product).

No case of overdose has been reported for Echinacea.

In conclusion, this product proves not to be harmful in the specified conditions of use based on the review of safetydata, expert report and additional data provided.

IV.3 Pharmacovigilance

It should be noted that in accordance with Article 16g of Directive 2001/83/EC, as amended, the pharmacovigilancerequirements described in Articles 101- 108 of Directive 2001/83/EC, as amended, also apply in respect of traditionalherbal medicinal products.

V OVERALL CONCLUSIONS

The important quality characteristics of the product are well-defined and controlled. Satisfactory pharmaceuticaldocumentation has been provided, assuring consistent quality of Echinaforce Sore Throat Spray.

The HPRA, on the basis of the data submitted, considered that Echinaforce Sore Throat Spray demonstrated adequateevidence of traditional use for the approved indication and no new preclinical or clinical safety concerns have beenidentified.

A certificate of traditional use registration for Echinaforce Sore Throat Spray is granted.


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